EBV-infected cell lineage by EBER double-staining as a diagnostic and prognostic clue in pediatric EBV-related lymphoproliferative disorders: a Japanese central pathology cohort study.

We retrospectively analyzed 36 children with Epstein-Barr virus-related lymphoproliferative disorder (EBV-LPD) from the Japan Children's Cancer Group (2006-2021), focusing on diagnostically challenging lesions not definitively classified as lymphoma. Using EBER in situ hybridization double-staining, we confirmed EBV infection primarily in T/NK cells (EBV-T/NK-LPD, n = 17) or B cells (EBV-B-LPD, n = 16). Lymphoid follicle architecture was effaced in EBV-T/NK-LPD (89%) and EBV-B-LPD (54%). 5-year overall survival was lower for EBV-T/NK-LPD (59%) than EBV-B-LPD (93%). Determining the EBV-infected cell lineage enables clinically relevant classification and risk stratification, and can be applied to archival specimens, including lesions initially interpreted as reactive.